1. Field of the Invention
The invention is directed to organ protectant solutions, and more particularly, to a solution which prevents or reduces in vivo lethal swelling of tissues and organs during periods of ischemia due to blood loss, trauma or shock, and the resulting lack of oxygen delivery to and oxygenation of tissues and organs. The invention is further directed to a method for treating individuals suffering from rapid blood loss, trauma or shock, thereby extending the period of time during which resuscitation and transportation of such individuals may be safely and successfully conducted in order to provide extended medical or surgical intervention and/or blood transfusion.
2. Prior Art
Initial therapy of trauma and hemorrhage shock centers on effective cessation of bleeding and on the infusion of large volumes (2 to 8 liters) to replace lost blood volume. This is considered necessary to restore normal circulatory functions such as arterial blood pressure, cardiac output, oxygen consumption and renal function. Conventionally, isotonic fluids are used for high volume resuscitation. Many cellular complications and practical limitations have been cited while using high volume fluids for resuscitation. When blood is lost, the greatest immediate need is to stop further blood loss, but the second greatest need is replacing the lost volume. If the fluid volume is maintained, remaining red blood cells may still be sufficient to circulate and oxygenate body tissues for a period of time. In this scenario, it may be possible to reduce or prevent ischemic injury if appropriate medical or surgical intervention can be accomplished.
Recently, resuscitation of hemorrhaged animals and injured patients has been performed with low volume hyperosmotic saline solutions with little success. Glucose or mannitol has been tested with less successful results. Small volume resuscitation has been successfully used in some cases using hyperoncotic albumins or high molecular weight tense state polymerized hemoglobins. The use of hypertonic saline solutions (HTS) or colloid solutions (albumin, HES, Hetastarch, Hextend) have had very limited success in clinical trauma and resuscitation, and, due to their mechanism of action, they do not prevent cell swelling. However, none of these procedures is known to be effective in preventing lethal cell swelling in vivo. Cells, organs, and tissues that suffer from lack of oxygen delivery, as occurs during traumatic shock and hemorrhagic hypovolemia, begin to swell with water because they lose energy dependent volume control mechanisms. In patients suffering from acute hemorrhagic shock and/or trauma, there is substantial intracellular oxygen deprivation, which in turn drops ATP concentration. Due to lack of ATP, the cellular sodium pump fails and free sodium enters the cell, followed by osmotic water movement. Movement of water into the cell causes swelling that leads to organ failure and death. Massive cell swelling further compresses the capillaries and sinusoids and impedes microcirculatory flow through organs and tissues even when the blood pressure is restored after hemorrhage. This is called the “no reflow phenomenon” and it occurs largely from local cell swelling.
This is particularly a problem in battlefield or civilian pre-hospital settings where large volumes cannot be carried and administered to patients in need of rapid paramedical intervention and transport to hospital or surgical treatment centers. There is a so-called “golden hour” of time during which restoration of blood volume and prevention of ischemic injury must be achieved to prevent catastrophic organ failure and death. There is no present day technology to deal with cell swelling and tissue damage to patients experiencing prolonged periods of shock and low volume resuscitation.